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Biomedical subjects

E Madon

Publications and source records attributed to E Madon.

At least 55 records · Page 3Linked to original sources
PubMed1994

Monitoring of cyclosporine blood levels from central venous lines: a misleading assay?

In order to assess the suspected influence of indwelling lines on the measurement of cyclosporine (CSA) blood levels, we evaluated CSA concentrations in samples drawn simultaneously from both silicone catheter lumens and peripheral veins of eight bone marrow transplant recipients. Blood samples were obtained at 30 min or 6-12 h after discontinuation of intravenous CSA. CSA concentrations were determined in whole blood by specific monoclonal antibody assay. Mean CSA levels from the lumen used for CSA administration were significantly higher than those from samples drawn from the second lumen (i.e., not used for CSA infusion) or peripheral vein. This difference, obtained when the infusion had been interrupted for 30 min, was still the case 6-12 h after discontinuation of CSA infusion. No difference was found between samples obtained from the second lumen and peripheral vein. These observations suggest that CSA might be adsorbed or bound by the silicon catheter and, thus, CSA blood level measurements may be misleading. The second lumen of the catheter or a peripheral vein should be used for accurate monitoring of CSA concentrations.

Adolescent↗
PubMed1994

[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study].

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.

Adolescent↗
PubMed1994

[Lipidemic alterations in a child with acute lymphoblastic leukemia in treatment with L-aspariginase].

The case of a child treated for Acute Lymphoblastic Leukemia (LLA) with high-dose L-asparaginase, (HD L-ase) presented alteration who of lipidemic values (rise of total cholesterol and triglyceride values) without toxicity is described. This finding has previously been reported in only a few patients. Parameters normalized with dietetic regimen. The authors underline the importance of the control, in patient during HD L-ase treatment of lipidic values too, especially when parents also have similar alterations.

Asparaginase↗
PubMed1993

Risk-directed therapy for childhood acute lymphoblastic leukemia. Results of the Associazione Italiana Ematologia Oncologia Pediatrica '82 studies.

BACKGROUND: In 1982, the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) started its third-generation study, aiming to improve previous results obtained by AIEOP '79 study and to deliver a standardized treatment to most Italian children with acute lymphoblastic leukemia (ALL). METHODS: We treated 902 children (older than 1 year and younger than 15 years of age) with newly diagnosed ALL in multicenter studies of risk-directed therapy (111 low risk [LR] from Study 8201; 570 average risk [AR] from Study 8202; and 117 and 104 high risk [HR] from Studies 8303 and 8503, respectively). Induction therapy was composed of vincristine, prednisone, and asparaginase for LR or AR patients and these agents plus daunorubicin, (Study 8503) or vincristine, prednisone, cytarabine, and intermediate-dose methotrexate (Study 8303) for HR patients. Central nervous system (CNS) preventive therapy consisted of intrathecal methotrexate only (LR), intrathecal methotrexate plus 18 Gy cranial irradiation (AR and HR Study 8503), or high-dose (HD) cytarabine (HR Study 8303). Reinduction therapy was vincristine/prednisone/daunorubicin for AR patients with cyclophosphamide added for HR patients in Study 8303 and HD asparaginase in Study 8503. LR patients did not receive intensification therapy. Continuation therapy comprised 6-mercaptopurine plus methotrexate and monthly pulses with vincristine plus prednisone for all patients, except for HR patients in Study 8303 who also received teniposide plus cytarabine. Weekly HD asparaginase was also given in Study 8503. Duration of treatment was 24 months for Studies 8201 and 8202, 15 months for Study 8303, and 22 months for Study 8503. The overall complete remission (CR) rate was 94.7% (97.3% for LR, 94.9% for AR, and 93.2% for HR). RESULTS: Overall 7-year event-free survival (EFS) was 53.6% (standard error [SE], 1.8). EFS was 60.8% in LR (SE, 4.7), 60.6% in AR at 7 years (SE, 4.7), and 18.5% in Study 8303 (HR) at 5 years (SE, 3.8). Because of the poor result in HR patients, a successor study (8503) was developed that yielded a 5-year EFS of 46.1% (SE, 5.1). Site-specific relapse rates were 18.5% (LR), 13.4% (AR), 35.1% (HR on 8303), and 18.3% (HR in Study 8503) for bone marrow and 9.2%, 7.9%, 17.5%, and 19.3%, respectively, for the CNS (isolated). Isolated testicular relapse was observed in 3.9% of male patients. CONCLUSIONS: This risk-directed therapy cured at least 50% of patients with ALL with relatively nonintensive therapy. The 80% overall survival rate for LR and AR patients at 7 years suggested that the total cure rate may be higher than 50% because of the significant salvage rate for patients who received antimetabolite-based therapy initially.

Adolescent↗
PubMed1993

Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group.

PURPOSE: This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS: From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS: Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION: The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.

Adolescent↗
PubMed1993

Human cord blood progenitors: kinetics, regulation and their use for hemopoietic reconstitution.

The high number of cord blood (CB) hematopoietic progenitors made possible CB transplantation in children with hematologic diseases. We collected and cryopreserved CB from siblings of 11 hematologic pediatric patients for possible transplant. The number of BFU-E+CFU-GEMM and CFU-GM was adequate for engraftment. However the possibility of CB transplantation in adolescents and adults is limited by the amount of CB that can be collected. We studied the possibility of expanding the pool of CB hematopoietic progenitors by preincubation of CB CD 34+ cells with several cytokines. After pre-exposition to rhIL-3, IL-1 beta, rIL-6, GM-CSF and stem cell factor (SCF) and cloning with SCF the number of hematopoietic progenitors increased 14-18 fold compared to basal values.

Blood Cell Count↗
PubMed1993

[Pulmonary complications after bone marrow transplantation].

Pulmonary toxicity occurs in approximately 10 to 50% of patients undergoing bone marrow transplantation (BMT). Bacterial pneumonia very commonly affects patients within the first 6 months post-BMT. Etiologic factors include neutropenia and the presence of graft-versus-host disease (GVHD). Pulmonary fungal infections, due to candida and aspergillus, may develop in 16% of patients receiving BMT, with a high mortality rate, being about 80%. A prolonged neutropenia as well as GVHD and associated immunosuppressive treatments are important factors in predisposing a patient to develop fungal pneumonitis. Interstitial pneumonitis occurs in 10-40% of patients; herpes viruses are the most commonly documented cause, with cytomegalovirus (CMV) being the most common pathogen. No causative organism is identified in up to 60% of the cases. It is likely that some of these cases may result from drug or radiation toxicity. Lung shielding and fractionation of the dose have decreased the incidence of interstitial pneumonitis to less than 5%. Patients with GVHD are predisposed to lung infections because of the immunosuppression that accompanies GVHD and its treatment. In addition, GVHD itself appears to have a direct effect on pulmonary epithelium. Cultural and serologic studies as well as radiographic investigations and other diagnostic procedures (ie bronchoalveolar lavage) are needed for appropriate management of pulmonary complications.

Bone Marrow Transplantation↗
PubMed1993

Rebound thymic hyperplasia following high dose chemotherapy and allogeneic BMT.

We describe a child with acute lymphoblastic leukemia who showed mediastinal widening 8 months after allogeneic BMT. Total thymectomy was carried out by the transcervical approach. Histologic examination showed only thymic hyperplasia. The immunohistologic investigation revealed a normal distribution of thymic cell elements, without evidence of clonal proliferation of lymphocytic subpopulations. This case supports the hypothesis that thymic hyperplasia following chemotherapy may be merely a rebound phenomenon. The patient had an uneventful postoperative recovery and remains in remission more than 1 year after BMT.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Monosomy 20 in childhood acute lymphoblastic leukemia.

We report two cases of acute lymphoblastic leukemia (ALL) with loss of chromosome 20 as the only karyotypic abnormality detected in the blast cells. The first patient is a 12-year-old boy studied at diagnosis. He represents the only case of monosomy 20 in our series of 90 pediatric ALL successfully karyotyped at diagnosis. In the second patient, monosomy 20 was detected at the second hematologic relapse, 12 years after the initial diagnosis; cytogenetic studies were not performed at disease onset.

Bone Marrow Cells↗
PubMed1992

[Hodgkin's disease in childhood].

Only in these latest years has been possible to consider Hodgkin disease (HD) as a neoplastic syndrome, thank of immunohistochemistry and cytogenetic techniques which have confirmed the monoclonal origin of typical cellular marker of disease: the Reed-Sternberg cell (R-S cell). Interesting associations have been observed between children suffering from HD and the positivity of EBV antigen above all in the socio-economically developed countries. The histopathologic classification of HD is divided in four sub-types, with different incidence in the pediatric age: the nodular sclerosis and the mixed cellularity are more rap-presented than the lymphocyte predominance and mostly the lymphocyte depletion. Histopathologic classification is essential for the prognosis and a correct therapeutic approach to disease. The management of HD is based on chemotherapy and radiotherapy associated; the results of treatment are more and more encouraging with a global survival over 95%. Sequelae of treatment are reduced in modern therapeutic trials: in particularly injury to somatic growth, cardiopulmonary system, gonadal and thyroid functionality is reduced by using low dose and involved fields for the early stage patients. The most important sequela in children treated for HD is the risk to developed a second malignant neoplasm; in particularly acute nonlymphocytic leukemia and non Hodgkin's lymphoma. In patients treated with radiotherapy alone increase the risk to develop solid tumors like sarcomas and carcinomas, which can appears several years after diagnosis.

Child↗
PubMed1992

[The leukemia-lymphoma syndrome with gastrointestinal involvement in childhood. A case report].

The gastrointestinal tract is an uncommon site of presentation for acute lymphoblastic leukemia in children. We report a child who developed a leukemia-lymphoma syndrome with central nervous system and gastrointestinal tract involvement at the diagnosis. The patient received an intensive combination chemotherapy and is currently off-therapy in continuous complete remission 29 months after the diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

ABMT for children AML: Italian experience. GITMO-AIEOP Groups.

We report data from an Italian survey on ABMT in 93 AML children less than 14 years in 1st or 2nd remission performed in 15 Centers. Different conditioning regimens have been employed: BAVC, an original schedule of chemotherapy; TBI plus Cy and/or other drugs (TBI + CHT); other high dose chemotherapy schedules (HD CHT). 62 patients have been transplanted in 1st CR; 38 have been conditioned with BAVC, 16 with TBI + CHT and 8 with HD CHT. Relapses were 21 in the BAVC group (DFS = 35% at 66 months), 5 in the TBI group (DFS = 61% at 48 months) and 5 in the HD CHT group; overall DFS is 39% at 66 months. 31 patients have been transplanted in 2nd CR; 14 were conditioned with BAVC and 16 with TBI + CHT; 6 patients relapsed in the first group, DFS is 56% at 50 months; in the second group 2 early deaths and 3 relapses occurred, DFS is 65% at 65 months. 1 patient in 2nd CR, conditioned with HD CHT, died during aplasia. Overall DFS is 59% at 65 months. Although no final conclusions concerning ABMT in AML children may be drawn from this retrospective study because of heterogeneity of population and methods, results obtained in 2nd CR are clearly better to those obtained with standard chemotherapy alone, confirming the role of ABMT in this high risk category of patients.

Adolescent↗